Nephrotic Syndrome, Focal Segmental Glomerulosclerosis, Minimal Change Disease
Conditions
Brief summary
The purpose of this study is evaluate if abatacept is effective and safe in decreasing the level of protein loss in the urine in patients with excessive loss of protein in the urine (nephrotic syndrome) due to either focal segmental glomerulosclerosis (FSGS) or minimal change disease (MCD). Candidates must have a prior kidney biopsy with either diagnosis. Another kidney biopsy will not be required as part of the study. Candidates must have failed or be intolerant of prior therapy for their kidney disease. The failed or intolerant therapy must include corticosteroids and at least one other drug. Candidates can be adults and children over the age of 6. Abatacept will be administered by venous infusion every 4 weeks.
Interventions
DRUGAbatacept
Abatacept IV administered on Day 1, 15, 29 and then every 28 days
OTHERNormal Saline
Normal Saline administer on Day 1, 15, 29 and then every 28 days
OTHERD5W
Dextrose 5% in Water (D5W) administered on Day 1, 15, 29 and then every 28 days
Sponsors
Bristol-Myers Squibb
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
6 Years to No maximum
Healthy volunteers
No
Inclusion criteria
For more information regarding BMS clinical trial participation, please visit www.BMSStudyConnect.com Inclusion Criteria: * Male and female subjects ages ≥ 6 years * Subjects resistant to corticosteroids, calcineurin inhibitors (cyclosporine and tacrolimus), sirolimus, mycophenolate mofetil (MMF), mycophenolic acid (MPA), or cyclophosphamide or intolerant to at least 2 of these * UPCR ≥ 3 at screening * FSGS or MCD confirmed by renal biopsy * eGFR ≥ 45 for children and adults * Concomitant use of angiotensin-converting-enzyme inhibitor (ACEi) or angiotensin receptor blocker (ARB) at stable doses for at least 2 weeks or have intolerance documented in the source documents maintained at the site
Exclusion criteria
* Kidney diseases other than FSGS or MCD * Collapsing FSGS * Systemic lupus erythematosus * Diabetes mellitus, both type 1 and type 2 * Clinically significant congestive heart failure * Post renal transplantation, including relapsing post-transplant FSGS * Body mass index (BMI): \> 40 in subjects ≥ 18 years of age and ≥ 99% percentile for subjects \< 18 years of age Other protocol defined inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants in Renal Response at Day 113 | From first dose to 113 days following first dose of the indicated period (113 days for Double-Blind Period, 226 days for Open Label Period) | Renal Response is defined as the presence of all the following criteria: PROTEINURIA: Reduction of baseline urine protein/creatinine ratio (UPCR) of \>= 50% and to less than 3. RENAL FUNCTION: No worsening of baseline estimated glomerular filtration rate (eGFR) defined as within normal range if normal at baseline or ≥ 75% baseline value if below normal at baseline. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change From Baseline in Serum Albumine at Day 113 | From baseline (measured at day 1 of the study) to 113 days following first dose administered in the indicated treatment period (113 days for Double-Blind Period, 226 days for Open Label Period) | — |
| Percentage of Participants Achieving Complete Remission at Day 113 | From first dose to 113 days following first dose of the indicated period (113 days for Double-Blind Period, 226 days for Open Label Period) | Complete Remission is defined as the presence of all the following criteria: PROTEINURIA: Urine protein/creatinine ratio (UPCR) ≤ 0.3. RENAL FUNCTION: No worsening of baseline estimated glomerular filtration rate (eGFR) defined as within normal range if normal at baseline or ≥ 75% baseline value if below normal at baseline. |
| Mean Change From Baseline in Patient Reported Outcomes Measurement Information System (PROMIS) at Day 113 - Adult Participants | From baseline (measured at day 1 of study) to 113 days following first dose administered in the Double-Blind Period | PROMIS was used to capture patient reported outcomes relevant to participants with nephrotic syndrome. Mean change from baseline is reported for the following measurements: Fatigue: Short From (SF) Fatigue v1.0 Adult 8a, composed of 8 questions, each one scored from 1 (Not at all) to 5 (Very much). Output presented as Total score, ranging from 8 (most desirable outcome) to 40 (least desirable outcome). Pain Interference: SF Pain Interference v1.0 Adult 8a, (measuring how much pain is interfering with daily activities). Composed of 8 questions, each one scored from 1 (Not at all) to 5 (Very much). Output presented as Total score, ranging from 8 (most desirable outcome) to 40 (least desirable outcome). Physical Function: SF Physical Function v1.2 Adult 8b, composed of 8 questions, each one scored from 1 (Without any difficulty) to 5 (Unable to do). Output presented as Total score, ranging from 8 (most desirable outcome) to 40 (least desirable outcome). |
| Mean Change From Baseline in Patient Reported Outcomes Measurement Information System (PROMIS) at Day 113 - Pediatric Participants | From baseline (measured at day 1 of study) to 113 days following first dose administered in the Double-Blind Period | PROMIS was used to capture patient reported outcomes relevant to participants with nephrotic syndrome. Mean change from baseline is reported for the following measurements: Fatigue: Short From (SF) Fatigue v1.0 Peds 10a, composed of 10 questions, each one scored from 0 (Never) to 4 (Almost Always). Output presented as Total score, ranging from 0 (most desirable outcome) to 40 (least desirable outcome). Pain Interference: SF Pain Interference v1.0 Peds 8a, ( measuring how much pain is interfering with daily activities). Composed of 8 questions, each one scored from 0 (Never) to 4 (Almost always). Output presented as Total score, ranging from 0 (most desirable outcome) to 32 (least desirable outcome). Mobility: SF Physical Function-Mobility v1.0 Peds 8a, composed of 8 questions, each one scored from 0 (Not able to do) to 4 (With no trouble). Output presented as Total score, ranging from 0 (least desirable outcome) to 32 (most desirable outcome). |
| Number of Participants Experiencing Adverse Events | From first dose in the indicated period to 56 days following last dose in the indicated period (169 days for the Double-Blind Period, up to 337 days for the Cumulative Abatacept Safety Period) | This outcome describes the number of participants experiencing various types of any grade Adverse Events (AEs). The Cumulative Abatacept Safety Period starts at the time of the first dose of Abatacept (either in the Double-Blind Period or in the Open Label Period) and lasts 56 days after the last dose of Abatacept |
| Number of Participants Experiencing Adverse Events of Special Interest | From first dose on day 1 to 56 days following last dose (approximately 330 days) | Number of participants experiencing various types of Adverse Events of interest, including infections, malignancies, autoimmune disorders, and infusional related reactions. |
| Mean Change From Baseline in Urine Protein/Creatinine Ratio (UPCR) at Day 113 | From baseline (measured at day 1 of study) to 113 days following first dose administered in the indicated treatment period (113 days for Double-Blind Period, 226 days for Open Label Period) | — |
| Minimum Blood Plasma Concentration (Cmin) of Abatacept - Adult Participants | From first dose to 113 days after first dose in the Double Blind Period. Data collected on day 15, day 29, day 57, day 85 and day 113 | — |
| Minimum Blood Plasma Concentration (Cmin) of Abatacept - Pediatric Participants | From first dose to 113 days after first dose in the Double Blind Period. Data collected on day 15, day 29, day 57, day 85 and day 113 | — |
| Maximum Observed Serum Concentration (Cmax) of Abatacept | Day 85 after first dose in the Double Blind Period | — |
| Area Under the Serum Concentration Time Curve Over a Dosing Interval (AUC(TAU)) of Abatacept | From Day 85 to Day 113 in the Double Blind Period | — |
| Time to Reach Peak Serum Concentration (Tmax(h)) of Abatacept | Day 85 after first dose in the Double Blind Period | — |
| Percentage of Participants With Positive Antibody Response Relative to Baseline | From baseline (day 1) to 168 days following last dose (up to 15 months). Results at day 113 from first dose, day 56, day 84 and day 168 after last dose are presented | A positive response relative to baseline is defined as a positive response at a post-baseline visit that has a titer value greater than the positive baseline titer value. If the baseline titer is missing or negative, any post-baseline positive titer value is considered a positive response relative to baseline. Immunogenicity response is presented as the total of immunogenicity response for CTLA4 and possibly Ig and Ig and/or Junction Region. |
Countries
United States
Participant flow
Pre-assignment details
36 participants were randomized and treated.
Participants by arm
| Arm | Count |
|---|---|
| Abatacept * Double Blind Periods 1 and 2 (DB1 and DB2): Abatacept IV administered on Day 1, 15, 29 and then every 28 days until the end of the Double Blind Period.
* Open Label Period (OLE): Abatacept IV administered every 28 days | 17 |
| Placebo * Double Blind Periods 1 and 2 (DB1 and DB2): Normal Saline or Dextrose 5% in Water (D5W) administered on Day 1, 15, 29 and then every 28 days until the end of the Double Blind Period.
* Open Label Period (OLE): Abatacept IV administered every 28 days | 19 |
| Total | 36 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Double-Blind Period 1 (DB1) | Adverse Event | 1 | 2 |
| Double-Blind Period 1 (DB1) | Lack of Efficacy | 1 | 3 |
| Double-Blind Period 1 (DB1) | No longer meeting study criteria | 0 | 1 |
| Double-Blind Period 1 (DB1) | Pregnancy | 1 | 0 |
| Double-Blind Period 2 (DB2) | Adverse Event | 1 | 0 |
| Double-Blind Period 2 (DB2) | Lack of Efficacy | 1 | 2 |
| Double-Blind Period 2 (DB2) | No longer meeting study criteria | 1 | 0 |
| Double-Blind Period 2 (DB2) | Other reasons | 1 | 0 |
| Double-Blind Period 2 (DB2) | Participant request to discontinue | 1 | 0 |
| Open Label Period (OLE) | Adverse Event | 0 | 1 |
| Open Label Period (OLE) | Lack of Efficacy | 3 | 5 |
| Open Label Period (OLE) | Lost to Follow-up | 0 | 1 |
| Open Label Period (OLE) | Other reasons | 0 | 2 |
| Open Label Period (OLE) | Participant request to discontinue | 1 | 0 |
| Transition From DB1 to DB2 | Skipped DB2 and moved into subsequent OLE | 3 | 2 |
| Transition From DB2 to OLE | Other reasons | 1 | 0 |
Baseline characteristics
| Characteristic | Placebo | Total | Abatacept |
|---|---|---|---|
| Age, Continuous | 28.7 Years STANDARD_DEVIATION 19.35 | 25.8 Years STANDARD_DEVIATION 16.8 | 22.5 Years STANDARD_DEVIATION 13.21 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 5 Participants | 7 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 14 Participants | 29 Participants | 15 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants | 7 Participants | 4 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants | 2 Participants | 0 Participants |
| Race (NIH/OMB) White | 14 Participants | 27 Participants | 13 Participants |
| Sex: Female, Male Female | 12 Participants | 20 Participants | 8 Participants |
| Sex: Female, Male Male | 7 Participants | 16 Participants | 9 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 17 | 0 / 19 | 0 / 11 | 0 / 11 | 0 / 23 |
| other Total, other adverse events | 13 / 17 | 15 / 19 | 7 / 11 | 8 / 11 | 16 / 23 |
| serious Total, serious adverse events | 5 / 17 | 4 / 19 | 0 / 11 | 2 / 11 | 6 / 23 |
Outcome results
Primary
Percentage of Participants in Renal Response at Day 113
Renal Response is defined as the presence of all the following criteria: PROTEINURIA: Reduction of baseline urine protein/creatinine ratio (UPCR) of \>= 50% and to less than 3. RENAL FUNCTION: No worsening of baseline estimated glomerular filtration rate (eGFR) defined as within normal range if normal at baseline or ≥ 75% baseline value if below normal at baseline.
Time frame: From first dose to 113 days following first dose of the indicated period (113 days for Double-Blind Period, 226 days for Open Label Period)
Population: All treated participants with available measurements
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Abatacept | Percentage of Participants in Renal Response at Day 113 | Double-Blind Period Day 113 | 0.0 Percent of Participants |
| Abatacept | Percentage of Participants in Renal Response at Day 113 | Open Label Period Day 113 | 12.5 Percent of Participants |
| Placebo | Percentage of Participants in Renal Response at Day 113 | Double-Blind Period Day 113 | 7.7 Percent of Participants |
| Placebo | Percentage of Participants in Renal Response at Day 113 | Open Label Period Day 113 | 33.3 Percent of Participants |
95% CI: [-46.8, 33.3]
95% CI: [-63.3, 24.3]
Secondary
Area Under the Serum Concentration Time Curve Over a Dosing Interval (AUC(TAU)) of Abatacept
Time frame: From Day 85 to Day 113 in the Double Blind Period
Population: All participants receiving Abatacept during the Double Blind Period with available measurements
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Abatacept | Area Under the Serum Concentration Time Curve Over a Dosing Interval (AUC(TAU)) of Abatacept | Adult participants | 20394.83 ug*h/mL | Geometric Coefficient of Variation 44.3 |
| Abatacept | Area Under the Serum Concentration Time Curve Over a Dosing Interval (AUC(TAU)) of Abatacept | Pediatric participants | 18282.50 ug*h/mL | Geometric Coefficient of Variation 41.9 |
Secondary
Maximum Observed Serum Concentration (Cmax) of Abatacept
Time frame: Day 85 after first dose in the Double Blind Period
Population: All participants receiving Abatacept during the Double Blind Period with available measurements
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Abatacept | Maximum Observed Serum Concentration (Cmax) of Abatacept | Adult participants | 200.46 ug/mL | Geometric Coefficient of Variation 43.9 |
| Abatacept | Maximum Observed Serum Concentration (Cmax) of Abatacept | Pediatric participants | 174.65 ug/mL | Geometric Coefficient of Variation 30 |
Secondary
Mean Change From Baseline in Patient Reported Outcomes Measurement Information System (PROMIS) at Day 113 - Adult Participants
PROMIS was used to capture patient reported outcomes relevant to participants with nephrotic syndrome. Mean change from baseline is reported for the following measurements: Fatigue: Short From (SF) Fatigue v1.0 Adult 8a, composed of 8 questions, each one scored from 1 (Not at all) to 5 (Very much). Output presented as Total score, ranging from 8 (most desirable outcome) to 40 (least desirable outcome). Pain Interference: SF Pain Interference v1.0 Adult 8a, (measuring how much pain is interfering with daily activities). Composed of 8 questions, each one scored from 1 (Not at all) to 5 (Very much). Output presented as Total score, ranging from 8 (most desirable outcome) to 40 (least desirable outcome). Physical Function: SF Physical Function v1.2 Adult 8b, composed of 8 questions, each one scored from 1 (Without any difficulty) to 5 (Unable to do). Output presented as Total score, ranging from 8 (most desirable outcome) to 40 (least desirable outcome).
Time frame: From baseline (measured at day 1 of study) to 113 days following first dose administered in the Double-Blind Period
Population: All treated participants with available measurements
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Abatacept | Mean Change From Baseline in Patient Reported Outcomes Measurement Information System (PROMIS) at Day 113 - Adult Participants | Fatigue | -5.56 Score on a scale | Standard Error 2.2907 |
| Abatacept | Mean Change From Baseline in Patient Reported Outcomes Measurement Information System (PROMIS) at Day 113 - Adult Participants | Pain Interference | -4.88 Score on a scale | Standard Error 2.6395 |
| Abatacept | Mean Change From Baseline in Patient Reported Outcomes Measurement Information System (PROMIS) at Day 113 - Adult Participants | Physical Function | 0.78 Score on a scale | Standard Error 1.735 |
| Placebo | Mean Change From Baseline in Patient Reported Outcomes Measurement Information System (PROMIS) at Day 113 - Adult Participants | Fatigue | -4.87 Score on a scale | Standard Error 2.6125 |
| Placebo | Mean Change From Baseline in Patient Reported Outcomes Measurement Information System (PROMIS) at Day 113 - Adult Participants | Pain Interference | -1.18 Score on a scale | Standard Error 3.9785 |
| Placebo | Mean Change From Baseline in Patient Reported Outcomes Measurement Information System (PROMIS) at Day 113 - Adult Participants | Physical Function | 1.77 Score on a scale | Standard Error 1.9346 |
95% CI: [-8.1395, 6.7645]
95% CI: [-13.9402, 6.5402]
95% CI: [-6.5736, 4.5736]
Secondary
Mean Change From Baseline in Patient Reported Outcomes Measurement Information System (PROMIS) at Day 113 - Pediatric Participants
PROMIS was used to capture patient reported outcomes relevant to participants with nephrotic syndrome. Mean change from baseline is reported for the following measurements: Fatigue: Short From (SF) Fatigue v1.0 Peds 10a, composed of 10 questions, each one scored from 0 (Never) to 4 (Almost Always). Output presented as Total score, ranging from 0 (most desirable outcome) to 40 (least desirable outcome). Pain Interference: SF Pain Interference v1.0 Peds 8a, ( measuring how much pain is interfering with daily activities). Composed of 8 questions, each one scored from 0 (Never) to 4 (Almost always). Output presented as Total score, ranging from 0 (most desirable outcome) to 32 (least desirable outcome). Mobility: SF Physical Function-Mobility v1.0 Peds 8a, composed of 8 questions, each one scored from 0 (Not able to do) to 4 (With no trouble). Output presented as Total score, ranging from 0 (least desirable outcome) to 32 (most desirable outcome).
Time frame: From baseline (measured at day 1 of study) to 113 days following first dose administered in the Double-Blind Period
Population: All treated participants with available measurements
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Abatacept | Mean Change From Baseline in Patient Reported Outcomes Measurement Information System (PROMIS) at Day 113 - Pediatric Participants | Fatigue | 6.43 Score on a scale | Standard Error 6.7142 |
| Abatacept | Mean Change From Baseline in Patient Reported Outcomes Measurement Information System (PROMIS) at Day 113 - Pediatric Participants | Pain Interference | 5.70 Score on a scale | Standard Error 3.9781 |
| Abatacept | Mean Change From Baseline in Patient Reported Outcomes Measurement Information System (PROMIS) at Day 113 - Pediatric Participants | Mobility | 0.80 Score on a scale | Standard Error 3.5007 |
| Placebo | Mean Change From Baseline in Patient Reported Outcomes Measurement Information System (PROMIS) at Day 113 - Pediatric Participants | Fatigue | -6.02 Score on a scale | Standard Error 3.6526 |
| Placebo | Mean Change From Baseline in Patient Reported Outcomes Measurement Information System (PROMIS) at Day 113 - Pediatric Participants | Pain Interference | -1.44 Score on a scale | Standard Error 1.918 |
| Placebo | Mean Change From Baseline in Patient Reported Outcomes Measurement Information System (PROMIS) at Day 113 - Pediatric Participants | Mobility | 1.68 Score on a scale | Standard Error 3.1905 |
95% CI: [-12.1068, 10.3468]
95% CI: [-4.595, 29.485]
95% CI: [-2.5917, 16.8717]
Secondary
Mean Change From Baseline in Serum Albumine at Day 113
Time frame: From baseline (measured at day 1 of the study) to 113 days following first dose administered in the indicated treatment period (113 days for Double-Blind Period, 226 days for Open Label Period)
Population: All treated participants with available measurements
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Abatacept | Mean Change From Baseline in Serum Albumine at Day 113 | Double-Blind Period Day 113 | 0.08 g/dL | Standard Error 0.1016 |
| Abatacept | Mean Change From Baseline in Serum Albumine at Day 113 | Open Label Period Day 113 | 0.21 g/dL | Standard Error 0.1829 |
| Placebo | Mean Change From Baseline in Serum Albumine at Day 113 | Double-Blind Period Day 113 | -0.05 g/dL | Standard Error 0.0892 |
| Placebo | Mean Change From Baseline in Serum Albumine at Day 113 | Open Label Period Day 113 | 0.09 g/dL | Standard Error 0.236 |
95% CI: [-0.1483, 0.4119]
95% CI: [-0.5107, 0.7551]
Secondary
Mean Change From Baseline in Urine Protein/Creatinine Ratio (UPCR) at Day 113
Time frame: From baseline (measured at day 1 of study) to 113 days following first dose administered in the indicated treatment period (113 days for Double-Blind Period, 226 days for Open Label Period)
Population: All treated participants with available measurements
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Abatacept | Mean Change From Baseline in Urine Protein/Creatinine Ratio (UPCR) at Day 113 | Double-Blind Period Day 113 | 0.12 mg/mg | Standard Error 0.5738 |
| Abatacept | Mean Change From Baseline in Urine Protein/Creatinine Ratio (UPCR) at Day 113 | Open Label Period Day 113 | 1.98 mg/mg | Standard Error 1.1598 |
| Placebo | Mean Change From Baseline in Urine Protein/Creatinine Ratio (UPCR) at Day 113 | Double-Blind Period Day 113 | -0.25 mg/mg | Standard Error 0.7914 |
| Placebo | Mean Change From Baseline in Urine Protein/Creatinine Ratio (UPCR) at Day 113 | Open Label Period Day 113 | 0.02 mg/mg | Standard Error 1.3049 |
95% CI: [-1.6495, 2.3855]
95% CI: [-1.7933, 5.6954]
Secondary
Minimum Blood Plasma Concentration (Cmin) of Abatacept - Adult Participants
Time frame: From first dose to 113 days after first dose in the Double Blind Period. Data collected on day 15, day 29, day 57, day 85 and day 113
Population: All adult participants receiving Abatacept during the Double Blind Period with available measurements
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Abatacept | Minimum Blood Plasma Concentration (Cmin) of Abatacept - Adult Participants | Day 15 | 7.613 ug/mL | Geometric Coefficient of Variation 63.7 |
| Abatacept | Minimum Blood Plasma Concentration (Cmin) of Abatacept - Adult Participants | Day 29 | 12.274 ug/mL | Geometric Coefficient of Variation 86.7 |
| Abatacept | Minimum Blood Plasma Concentration (Cmin) of Abatacept - Adult Participants | Day 57 | 3.641 ug/mL | Geometric Coefficient of Variation 66.5 |
| Abatacept | Minimum Blood Plasma Concentration (Cmin) of Abatacept - Adult Participants | Day 85 | 4.101 ug/mL | Geometric Coefficient of Variation 52.7 |
| Abatacept | Minimum Blood Plasma Concentration (Cmin) of Abatacept - Adult Participants | Day 113 | 2.786 ug/mL | Geometric Coefficient of Variation 68.2 |
Secondary
Minimum Blood Plasma Concentration (Cmin) of Abatacept - Pediatric Participants
Time frame: From first dose to 113 days after first dose in the Double Blind Period. Data collected on day 15, day 29, day 57, day 85 and day 113
Population: All pediatric participants receiving Abatacept during the Double Blind Period with available measurements
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Abatacept | Minimum Blood Plasma Concentration (Cmin) of Abatacept - Pediatric Participants | Day 15 | 2.829 ug/mL | Geometric Coefficient of Variation 116.4 |
| Abatacept | Minimum Blood Plasma Concentration (Cmin) of Abatacept - Pediatric Participants | Day 29 | 2.588 ug/mL | Geometric Coefficient of Variation 138.7 |
| Abatacept | Minimum Blood Plasma Concentration (Cmin) of Abatacept - Pediatric Participants | Day 57 | 0.504 ug/mL | Geometric Coefficient of Variation 143.2 |
| Abatacept | Minimum Blood Plasma Concentration (Cmin) of Abatacept - Pediatric Participants | Day 85 | 1.617 ug/mL | Geometric Coefficient of Variation 123.5 |
| Abatacept | Minimum Blood Plasma Concentration (Cmin) of Abatacept - Pediatric Participants | Day 113 | 0.990 ug/mL | Geometric Coefficient of Variation 163.1 |
Secondary
Number of Participants Experiencing Adverse Events
This outcome describes the number of participants experiencing various types of any grade Adverse Events (AEs). The Cumulative Abatacept Safety Period starts at the time of the first dose of Abatacept (either in the Double-Blind Period or in the Open Label Period) and lasts 56 days after the last dose of Abatacept
Time frame: From first dose in the indicated period to 56 days following last dose in the indicated period (169 days for the Double-Blind Period, up to 337 days for the Cumulative Abatacept Safety Period)
Population: All treated participants
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Abatacept | Number of Participants Experiencing Adverse Events | Adverse Events (AEs) | 13 Participants |
| Abatacept | Number of Participants Experiencing Adverse Events | Serious Adverse Events (SAEs) | 5 Participants |
| Abatacept | Number of Participants Experiencing Adverse Events | AEs leading to discontinuation | 1 Participants |
| Abatacept | Number of Participants Experiencing Adverse Events | Deaths | 0 Participants |
| Placebo | Number of Participants Experiencing Adverse Events | Deaths | 0 Participants |
| Placebo | Number of Participants Experiencing Adverse Events | Adverse Events (AEs) | 15 Participants |
| Placebo | Number of Participants Experiencing Adverse Events | AEs leading to discontinuation | 2 Participants |
| Placebo | Number of Participants Experiencing Adverse Events | Serious Adverse Events (SAEs) | 4 Participants |
| Abatacept During Cumulative Abatacept Safety Period | Number of Participants Experiencing Adverse Events | Deaths | 0 Participants |
| Abatacept During Cumulative Abatacept Safety Period | Number of Participants Experiencing Adverse Events | Serious Adverse Events (SAEs) | 10 Participants |
| Abatacept During Cumulative Abatacept Safety Period | Number of Participants Experiencing Adverse Events | AEs leading to discontinuation | 2 Participants |
| Abatacept During Cumulative Abatacept Safety Period | Number of Participants Experiencing Adverse Events | Adverse Events (AEs) | 26 Participants |
Secondary
Number of Participants Experiencing Adverse Events of Special Interest
Number of participants experiencing various types of Adverse Events of interest, including infections, malignancies, autoimmune disorders, and infusional related reactions.
Time frame: From first dose on day 1 to 56 days following last dose (approximately 330 days)
Population: All treated participants
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Abatacept | Number of Participants Experiencing Adverse Events of Special Interest | AE within 24 hours of Infusion | 8 Participants |
| Abatacept | Number of Participants Experiencing Adverse Events of Special Interest | Infections/Infestations | 12 Participants |
| Abatacept | Number of Participants Experiencing Adverse Events of Special Interest | Malignancies | 0 Participants |
| Abatacept | Number of Participants Experiencing Adverse Events of Special Interest | Autoimmune disorders | 0 Participants |
| Abatacept | Number of Participants Experiencing Adverse Events of Special Interest | Peri-infusional Adverse Event (AE) | 6 Participants |
| Placebo | Number of Participants Experiencing Adverse Events of Special Interest | Autoimmune disorders | 1 Participants |
| Placebo | Number of Participants Experiencing Adverse Events of Special Interest | Peri-infusional Adverse Event (AE) | 3 Participants |
| Placebo | Number of Participants Experiencing Adverse Events of Special Interest | AE within 24 hours of Infusion | 9 Participants |
| Placebo | Number of Participants Experiencing Adverse Events of Special Interest | Malignancies | 0 Participants |
| Placebo | Number of Participants Experiencing Adverse Events of Special Interest | Infections/Infestations | 10 Participants |
Secondary
Percentage of Participants Achieving Complete Remission at Day 113
Complete Remission is defined as the presence of all the following criteria: PROTEINURIA: Urine protein/creatinine ratio (UPCR) ≤ 0.3. RENAL FUNCTION: No worsening of baseline estimated glomerular filtration rate (eGFR) defined as within normal range if normal at baseline or ≥ 75% baseline value if below normal at baseline.
Time frame: From first dose to 113 days following first dose of the indicated period (113 days for Double-Blind Period, 226 days for Open Label Period)
Population: All treated participants with available measurements
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Abatacept | Percentage of Participants Achieving Complete Remission at Day 113 | Double-Blind Period Day 113 | 0.0 Percent of Participants |
| Abatacept | Percentage of Participants Achieving Complete Remission at Day 113 | Open Label Period Day 113 | 12.5 Percent of Participants |
| Placebo | Percentage of Participants Achieving Complete Remission at Day 113 | Double-Blind Period Day 113 | 0.0 Percent of Participants |
| Placebo | Percentage of Participants Achieving Complete Remission at Day 113 | Open Label Period Day 113 | 11.1 Percent of Participants |
95% CI: [-44.7, 44.7]
Secondary
Percentage of Participants With Positive Antibody Response Relative to Baseline
A positive response relative to baseline is defined as a positive response at a post-baseline visit that has a titer value greater than the positive baseline titer value. If the baseline titer is missing or negative, any post-baseline positive titer value is considered a positive response relative to baseline. Immunogenicity response is presented as the total of immunogenicity response for CTLA4 and possibly Ig and Ig and/or Junction Region.
Time frame: From baseline (day 1) to 168 days following last dose (up to 15 months). Results at day 113 from first dose, day 56, day 84 and day 168 after last dose are presented
Population: All treated participants with available measurements
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Abatacept | Percentage of Participants With Positive Antibody Response Relative to Baseline | Day 113 from first dose | 7.1 Percent of Participants |
| Abatacept | Percentage of Participants With Positive Antibody Response Relative to Baseline | Day 56 from last dose | 40.0 Percent of Participants |
| Abatacept | Percentage of Participants With Positive Antibody Response Relative to Baseline | Day 84 from last dose | 28.6 Percent of Participants |
| Abatacept | Percentage of Participants With Positive Antibody Response Relative to Baseline | Day 168 from last dose | 16.7 Percent of Participants |
| Placebo | Percentage of Participants With Positive Antibody Response Relative to Baseline | Day 168 from last dose | 25.0 Percent of Participants |
| Placebo | Percentage of Participants With Positive Antibody Response Relative to Baseline | Day 113 from first dose | 0.0 Percent of Participants |
| Placebo | Percentage of Participants With Positive Antibody Response Relative to Baseline | Day 84 from last dose | 66.7 Percent of Participants |
| Placebo | Percentage of Participants With Positive Antibody Response Relative to Baseline | Day 56 from last dose | 66.7 Percent of Participants |
Secondary
Time to Reach Peak Serum Concentration (Tmax(h)) of Abatacept
Time frame: Day 85 after first dose in the Double Blind Period
Population: All participants receiving Abatacept during the Double Blind Period with available measurements
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Abatacept | Time to Reach Peak Serum Concentration (Tmax(h)) of Abatacept | Adult participants | 0.883 Hours | Standard Deviation 0.242 |
| Abatacept | Time to Reach Peak Serum Concentration (Tmax(h)) of Abatacept | Pediatric participants | 0.589 Hours | Standard Deviation 0.285 |